Johanna Bendell, MD: Let’s talk about the future. Let’s talk about the exciting stuff, right? So, we’ve made some changes for patients. We’ve been able to, now, sequence treatments in the metastatic setting and we’ve got more options in the neoadjuvant setting. But what’s going to really break through for us for pancreas cancer? Where are some of the new, hot, treatments? Tell us a little bit about immunotherapy for patients with pancreatic cancer.

John Marshall, MD: I wish I had an exciting story to tell you in this space. We continue to be frustrated, with no subgroup coming out of this patient base. In almost every other gastrointestinal cancer, we found some subgroup responding. But we really have not yet seen this in pancreatic cancer. We’ve seen little bits here and there (an occasional benefit), but nothing that’s a steady drumbeat. We’re pretty sure that there will be something, but what’s the problem? Are they not immunogenic? Is it the stromal core that’s keeping any T cell from even getting there? Is this a physical problem?

We talked earlier about not understanding the genetics. It’s always the same mutations in all of these cancers, so maybe they’re not making the neoantigens that we need to make and that we’ve seen in other cancers? This does not mean that we should give up. But I will have to say that even through this meeting and others, I don’t see a lot of new projects either. People are learning that there are some out there. But at least for now, we need to keep working on it.

Our work now is around vaccines and in trying to drive the immune system up (now that we have these checkpoint-kind of approaches). So, I think it’s still very important for us to study, in this space, getting more tissue. And understanding the biology better will help, I think. But for me at least, and I’d love to hear what others have to say, I haven’t really seen anything that wows me yet.

Johanna Bendell, MD: Yes. So, outside of the incredibly rare microsatellite in a stable patient that you may find on your hunt, in immunotherapies, has anybody heard of any promising immunotherapy for pancreas cancer?

Eileen O’Reilly, MD: I think it’s pretty clear that the single-agent strategy is not for pancreas cancer patients. But I think there’s still some optimism that we can figure this out, at least for a subset of patients. And it’s clearly going to be through combination-based approaches. I think building on chemotherapy (because we know that works in this disease), may be something that we need to understand the pros and cons of. And maybe different settings, right? Maybe it’s a maintenance approach, maybe it’s post adjuvant, or maybe it’s after debulking in locally advanced disease. I don’t know.

John Marshall, MD: I’d look forward to seeing some of the trials. We’ve participated in the frontline setting—gemcitabine and nab-paclitaxel, plus a checkpoint inhibitor. And we were all very excited because there were lots of tumor marker responses and lots of clinical responses. But I’ve not yet seen, in at least our group, that durable response. So, they’re getting there. They’re having more responses, but they’re turning it 4, 5, 6 months (just like you would expect with traditional chemotherapy). So, I’d like to see the dataset as a whole. We were optimistic there for a while, and we’ve kind of gotten a little less optimistic.

George Kim, MD: How about cobimetinib?

Johanna Bendell, MD: What George is alluding to is the data from colon cancer where you’re using a MEK inhibitor in combination with a checkpoint inhibitor. Certainly, it would be the next logical thing to go to. I might have heard that there may be somebody that’s thinking about studying that.

Eileen O’Reilly, MD: It’s open, it’s happening.

Johanna Bendell, MD: Okay. I think you guys have all alluded to it. It’s going to be the combination therapies. There’s a lot of new immune targets that are coming down the pipeline, and I’ve heard little whispers about other things that are coming as well. And then there’s one agent, an IL-2 agonist, trying to bring T cells in, but I think it’s about to move into a randomized chemotherapy combination study. But I think for the practicing oncologist out there whose patient comes in and says, “I want that—what Jimmy Carter had,” because we have this all the time, it’s really hard to explain to them that’s probably not the right thing to do and to suggest that we try something else along the way.

Transcript Edited for Clarity

Transcript:

Johanna Bendell, MD: Let’s talk about the future. Let’s talk about the exciting stuff, right? So, we’ve made some changes for patients. We’ve been able to, now, sequence treatments in the metastatic setting and we’ve got more options in the neoadjuvant setting. But what’s going to really break through for us for pancreas cancer? Where are some of the new, hot, treatments? Tell us a little bit about immunotherapy for patients with pancreatic cancer.

John Marshall, MD: I wish I had an exciting story to tell you in this space. We continue to be frustrated, with no subgroup coming out of this patient base. In almost every other gastrointestinal cancer, we found some subgroup responding. But we really have not yet seen this in pancreatic cancer. We’ve seen little bits here and there (an occasional benefit), but nothing that’s a steady drumbeat. We’re pretty sure that there will be something, but what’s the problem? Are they not immunogenic? Is it the stromal core that’s keeping any T cell from even getting there? Is this a physical problem?

We talked earlier about not understanding the genetics. It’s always the same mutations in all of these cancers, so maybe they’re not making the neoantigens that we need to make and that we’ve seen in other cancers? This does not mean that we should give up. But I will have to say that even through this meeting and others, I don’t see a lot of new projects either. People are learning that there are some out there. But at least for now, we need to keep working on it.

Our work now is around vaccines and in trying to drive the immune system up (now that we have these checkpoint-kind of approaches). So, I think it’s still very important for us to study, in this space, getting more tissue. And understanding the biology better will help, I think. But for me at least, and I’d love to hear what others have to say, I haven’t really seen anything that wows me yet.

Johanna Bendell, MD: Yes. So, outside of the incredibly rare microsatellite in a stable patient that you may find on your hunt, in immunotherapies, has anybody heard of any promising immunotherapy for pancreas cancer?

Eileen O’Reilly, MD: I think it’s pretty clear that the single-agent strategy is not for pancreas cancer patients. But I think there’s still some optimism that we can figure this out, at least for a subset of patients. And it’s clearly going to be through combination-based approaches. I think building on chemotherapy (because we know that works in this disease), may be something that we need to understand the pros and cons of. And maybe different settings, right? Maybe it’s a maintenance approach, maybe it’s post adjuvant, or maybe it’s after debulking in locally advanced disease. I don’t know.

John Marshall, MD: I’d look forward to seeing some of the trials. We’ve participated in the frontline setting—gemcitabine and nab-paclitaxel, plus a checkpoint inhibitor. And we were all very excited because there were lots of tumor marker responses and lots of clinical responses. But I’ve not yet seen, in at least our group, that durable response. So, they’re getting there. They’re having more responses, but they’re turning it 4, 5, 6 months (just like you would expect with traditional chemotherapy). So, I’d like to see the dataset as a whole. We were optimistic there for a while, and we’ve kind of gotten a little less optimistic.

George Kim, MD: How about cobimetinib?

Johanna Bendell, MD: What George is alluding to is the data from colon cancer where you’re using a MEK inhibitor in combination with a checkpoint inhibitor. Certainly, it would be the next logical thing to go to. I might have heard that there may be somebody that’s thinking about studying that.

Eileen O’Reilly, MD: It’s open, it’s happening.

Johanna Bendell, MD: Okay. I think you guys have all alluded to it. It’s going to be the combination therapies. There’s a lot of new immune targets that are coming down the pipeline, and I’ve heard little whispers about other things that are coming as well. And then there’s one agent, an IL-2 agonist, trying to bring T cells in, but I think it’s about to move into a randomized chemotherapy combination study. But I think for the practicing oncologist out there whose patient comes in and says, “I want that—what Jimmy Carter had,” because we have this all the time, it’s really hard to explain to them that’s probably not the right thing to do and to suggest that we try something else along the way.